Drug Mechanism, Healthy
Conditions
Keywords
electrochemical, Paracetamol, Lipidomics, Endocannabinoid system
Brief summary
The main objective is to assess whether a novel electrochemical tool is reliable in detecting concentration of paracetamol in fingerprick- , saline-, urine-, and serum samples. We will recruit 12 healthy volunteers aged 18-45. They will get 1 g oral paracetamol. Paracetamol concentration will be detected from abovementioned samples at timely intervals for 24 hours, analyzed with the novel electrochemical method and compared to gold standard mass-spectrometry analysis. Despite of extensive use, the mechanism of action of parasetamol is not completely understood. The central serotonergic system may play a role. Endocannabinoid system is a group of lipid mediators, that possibly is involved in mediating paracetamol effect to the serotonergic system. Serum lipidomic assessment can be used to study endocannabinoid metabolics. In this study we will try to assess changes in endocannabinoid system by looking into serum lipidomics in order to understand the mechanism of action of paracetamol.
Interventions
DRUGParacetamol
1 g oral paractamol
DIAGNOSTIC_TESTParacetamol concentration measurements and lipidomic assessment
Paracetamol concentration is measured from saline-, urine-, venous blood- and fingerprick- samples at timely intervals. Also serum lipidomic assessment is performed from venous blood samples.
Sponsors
Johanna Kujala
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
Healthy volunteers
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy, no medication of any kind. * Age 18-45 * BMI 18.5 - 30 * Informed consent
Exclusion criteria
* Pregnancy, lactation. * prisoner * smoking * less than 3 months from prior blood donation or clinical pharmacological study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of Geometric Means of Cmax and AUC 0-last of Paracetamol Measured by the Novel Electrochemical Method With Mass-spectrometry in Capillary Whole Blood Samples. | 1 day | Geometric mean values of the highest paracetamol concentrations (Cmax) and area under the curve (AUC) measured with the novel electrochemical method were compared with the 'gold standard' mass-spectrometry (control) from capillary whole blood samples. The data are presented as the ratio of geometric means to control, geometric coefficients of variation (as percentage) as a measure of dispersion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of Geometric Means of Cmax and AUC 0-last of Paracetamol in Capillary With Venous Plasma (Control), Both Measured by Mass-spectrometry. | 12 hours | Geometric mean values of the highest paracetamol concentrations (Cmax) and area under the curve -calculations (AUC0-last) measured by mass-spectrometry were compared between capillary and plasma (control) to analyse paracetamol pharmacokinetics. The data are presented as ratio-to-control with geometric coefficients of variation (as percentage). |
Countries
Finland
Participant flow
Recruitment details
Recruitment was announced on Helsinki University student's website in January 2021.
Pre-assignment details
No medications or nutritional supplements were allowed prior to the study day.
Participants by arm
| Arm | Count |
|---|---|
| Study Group All healthy volunteers are in this group. They receive 1g paracetamol orally. Saline-, urine-, venous blood and fingerprick samples will be collected at timely intervals.
Paracetamol: 1 g oral paractamol
Paracetamol concentration measurements and lipidomic assessment: Paracetamol concentration is measured from saline-, urine-, venous blood- and fingerprick- samples at timely intervals. Also serum lipidomic assessment is performed from venous blood samples. | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Study Group |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment Finland | 12 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 12 |
| other Total, other adverse events | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
Comparison of Geometric Means of Cmax and AUC 0-last of Paracetamol Measured by the Novel Electrochemical Method With Mass-spectrometry in Capillary Whole Blood Samples.
Geometric mean values of the highest paracetamol concentrations (Cmax) and area under the curve (AUC) measured with the novel electrochemical method were compared with the 'gold standard' mass-spectrometry (control) from capillary whole blood samples. The data are presented as the ratio of geometric means to control, geometric coefficients of variation (as percentage) as a measure of dispersion.
Time frame: 1 day
Population: All healthy volunteers in this group.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cmax | Comparison of Geometric Means of Cmax and AUC 0-last of Paracetamol Measured by the Novel Electrochemical Method With Mass-spectrometry in Capillary Whole Blood Samples. | 1.03 ratio-to-control | Geometric Coefficient of Variation 21 |
| AUC 0-last | Comparison of Geometric Means of Cmax and AUC 0-last of Paracetamol Measured by the Novel Electrochemical Method With Mass-spectrometry in Capillary Whole Blood Samples. | 1.17 ratio-to-control | Geometric Coefficient of Variation 29 |
Comparison: Highest paracetamol concentrations (Cmax) measured from capillary with the electrochemical method compared with measurements with mass-spectrometry.p-value: 0.0590% CI: [0.94, 1.13]t-test, 2 sided
Secondary
Comparison of Geometric Means of Cmax and AUC 0-last of Paracetamol in Capillary With Venous Plasma (Control), Both Measured by Mass-spectrometry.
Geometric mean values of the highest paracetamol concentrations (Cmax) and area under the curve -calculations (AUC0-last) measured by mass-spectrometry were compared between capillary and plasma (control) to analyse paracetamol pharmacokinetics. The data are presented as ratio-to-control with geometric coefficients of variation (as percentage).
Time frame: 12 hours
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cmax | Comparison of Geometric Means of Cmax and AUC 0-last of Paracetamol in Capillary With Venous Plasma (Control), Both Measured by Mass-spectrometry. | 1.50 ratio-to-control | Geometric Coefficient of Variation 31 |
| AUC 0-last | Comparison of Geometric Means of Cmax and AUC 0-last of Paracetamol in Capillary With Venous Plasma (Control), Both Measured by Mass-spectrometry. | 1.08 ratio-to-control | Geometric Coefficient of Variation 30 |